rs9289798

Variant names:

• chr3-150004607-T-G
• rs9289798
• ENST00000494827.5:c.-16+18013A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000494827.5(PFN2):​c.-16+18013A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,918 control chromosomes in the GnomAD database, including 7,460 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7460 hom., cov: 31)
• Consequence: PFN2 ENST00000494827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712
• Publications: 6 publications found

Genes affected

PFN2 (HGNC:8882): (profilin 2) The protein encoded by this gene is a ubiquitous actin monomer-binding protein belonging to the profilin family. It is thought to regulate actin polymerization in response to extracellular signals. There are two alternatively spliced transcript variants encoding different isoforms described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFN2	ENST00000494827.5	c.-16+18013A>C		intron_variant	Intron 1 of 2	4		ENSP00000418523.1
PFN2	ENST00000497148.5	c.-15-36057A>C		intron_variant	Intron 1 of 2	4		ENSP00000417817.1
PFN2	ENST00000649949.1	c.-16+16348A>C		intron_variant	Intron 2 of 3			ENSP00000498146.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47477 AN: 151800 Hom.: 7461 Cov.: 31

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.313 AC: 47500 AN: 151918 Hom.: 7460 Cov.: 31 AF XY: 0.313 AC XY: 23224 AN XY: 74252

African (AFR) AF: 0.351 AC: 14541 AN: 41410

American (AMR) AF: 0.351 AC: 5347 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3468

East Asian (EAS) AF: 0.262 AC: 1353 AN: 5158

South Asian (SAS) AF: 0.312 AC: 1503 AN: 4812

European-Finnish (FIN) AF: 0.269 AC: 2843 AN: 10570

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19725 AN: 67944

Other (OTH) AF: 0.327 AC: 690 AN: 2112

Alfa AF: 0.301 Hom.: 5535

Bravo AF: 0.318

Asia WGS AF: 0.308 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.70
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9289798; hg19: chr3-149722394;